Polypeptide fragments of fibronectin which can modulate extracellular matrix assembly

Abstract

In accordance with the present invention, there is provided a novel synthetic polypeptide derived from the first type III repeat of fibronectin. The synthetic polypeptide of the invention encompasses a fibronectin-fibronectin binding site, and is capable of inhibiting fibronectin matrix assembly. In contrast to previously identified fibronectin fragments that block fibronectin matrix assembly by blocking an initial event in matrix assembly (i.e., fibronectin binding to cells), the invention polypeptide appears to inhibit an intermediate step in matrix assembly, i.e., fibronectin self-association prior to the disulfide cross-linking that stabilizes the fibronectin matrix.

That which is claimed is: 
     
       1. A substantially purified polypeptide related to the III I  repeat of fibronectin comprising the amino acid sequence set forth in SEQ ID NO: 1 and having a molecular weight of about 14 kDa, wherein said polypeptide has the ability to bind to fibronectin directly and to substantially reduce fibronectin matrix assembly, while not reducing substantially the ability of fibronectin to bind to cells. 
     
     
       2. A polypeptide according to claim 1, wherein said polypeptide is further characterized by: being capable of inhibiting fibronectin-fibronectin association.   
     
     
       3. A polypeptide according to claim 1, wherein said polypeptide is further characterized by: binding specifically to IMR-90 cells, but not to HT-1080 cells.   
     
     
       4. A substantially purified polypeptide related to the III I  repeat of fibronectin having a molecular weight of about 14 kDa and having the amino acid sequence set forth in SEQ ID NO: 1, wherein said polypeptide has the ability to bind to fibronectin directly and to substantially reduce fibronectin matrix assembly, while not reducing substantially the ability of fibronectin to bind to cells. 
     
     
       5. A polypeptide fragment of a 14 kDa polypeptide related to the II I  repeat of fibronectin, wherein said fragment is selected from the group consisting of P1, P2, P3, and P4, wherein P1 has the amino acid sequence shown in SEQ ID NO: 2; P2 has the amino acid sequence shown in SEQ ID NO: 3; P3 has the amino acid sequence shown in SEQ ID NO: 4; and P4 has the amino acid sequence shown in SEQ ID NO: 5. 
     
     
       6. A composition comprising at least two of the peptides of claim 5.